慢性乙型肝炎新型治疗药物研究进展

Advance on novel therapeutic agents for chronic hepatitis B

慢性乙型肝炎(慢乙肝)治疗的理想目标是功能性治愈。目前药物抗病毒治疗可以抑制病毒复制,减轻或消除肝脏病理损害,有效阻止向肝硬化和肝癌的进展,但不能清除HBs Ag和病毒库,所以难以达到临床治愈(或功能性治愈)。因此,须要针对HBV生命周期以及调节免疫系统研发新型抗病毒药物。近年来,HBV受体的发现以及HBV感染细胞体外培养模型的初步建立有利于研发潜在的抗病毒表面抗原或提高病毒特异性细胞免疫等宿主抗病毒药物,包括抑制HBsAg合成和病毒库的清除等。由此相信未来慢乙肝的功能性治愈可以通过联合免疫调节、抗病毒(HBV DNA、HBsAg)和共价闭合环状DNA抑制剂等治疗方案来现实。

The ideal goal for chronic hepatitis B is functional cure. The current antiviral treatment can efficiently control viral replication, reduce or eliminate liver pathological lesion, effectively prevent the progression into liver cirrhosis and liver cancer, but it cannot clear HBsAg and viral reservoir （cccDNA）. So it is still quite far from achieving a functional cure. Therefore, novel antiviral agents are needed to target various processes of hepatitis B virus lifecycle and regulate immune system. The emergency of HBV receptor and the establishment of in vitro HBV-infected cell-culture model will promote the development of potential antiviral surface antigen or incrrease virus-specific cellular immunity and other host antiviral drugs, such as inhibiting HBsAg synthesis and clearing viral reservoir. It is likely that successful HBV functional cure may be ultimately realized with the combinational use of HBV-specific immunomodulatory drugs, antiviral （HBsAg and HBV DNA） agents and cccDNA inhibitors.